910
Psychopharmacological Treatment
29
▲▲
29.1 General Principles of
Psychopharmacology
Psychopharmacologic advances continue to dramatically
expand the parameters of psychiatric treatments. Greater under-
standing of how the brain functions has led to more effective,
less toxic, better-tolerated, and more specifically targeted thera-
peutic agents. With the ever-increasing sophistication and array
of treatment options, clinicians, however, must remain aware of
potential adverse effects, drug–drug (and drug–food or drug–
supplement) interactions, and how to manage the emergence of
unwanted or unintended consequences. Newer drugs could ulti-
mately lead to side effects that are not recognized initially. Keep-
ing up with the latest research findings is increasingly important
as these findings proliferate. A thorough understanding of the
management of medication-induced side effects (either through
treating the effect with another agent or substituting another pri-
mary agent) is necessary.
Classification
Medications used to treat psychiatric disorders are referred to
as
psychotropic drugs.
These drugs are commonly described by
their major clinical application, for example,
antidepressants,
antipsychotics, mood stabilizers,
anxiolytics,
hypnotics,
cogni-
tive enhancers,
and
stimulants.
A problem with this approach
is that, in many instances, drugs have multiple indications. For
example, drugs such as the selective serotonin reuptake inhibi-
tors (SSRIs) are both antidepressants and anxiolytics, and the
serotonin-dopamine antagonists (SDAs) are both antipsychotics
and mood stabilizers.
Psychotropic drugs have also been organized according to
structure (e.g., tricyclic), mechanism (e.g., monoamine oxidase
inhibitor [MAOI]), history (e.g., first generation, traditional),
uniqueness (e.g., atypical), or indication (e.g., antidepressant).
A further problem is that many drugs used to treat medical and
neurological conditions are routinely used to treat psychiatric
disorders.
In addition, psychotropic drug terminology can be confus-
ing. The first pharmaceutical agents used to treat schizophre-
nia were termed
tranquilizers.
When newer drugs emerged as
therapies for anxiety, a distinction was drawn between
major
and
minor tranquilizers.
At first, antidepressants were tricyclic
antidepressants (TCAs) or MAOIs. In the 1970s and 1980s,
as newer antidepressant drugs emerged, they were labeled as
second-
or
third-generation antidepressants.
More recently,
older agents used as treatments for psychosis became known as
typical,
conventional,
or
traditional
neuroleptics. Newer ones
became
atypical neuroleptics.
In order to eliminate much of
this confusion, in this section, drugs are presented according
to shared mechanism of action or by similarity of structure to
provide consistency, ease of reference, and comprehensiveness.
Pharmacological Actions
Both genetic and environmental factors influence individual
response to, and tolerability of, psychotropic agents. Thus, a
drug that may not prove effective in many patients with a dis-
order can dramatically improve symptoms in others. In these
cases, identification of characteristics that might predict poten-
tial candidates for that drug becomes important, but often
remains elusive.
Drugs, even within the same class, are distinguished from
one another by often subtle differences in molecular structure,
types of interactions with neurotransmitter systems, differences
in pharmacokinetics, the presence or absence of active metabo-
lites, and protein binding. These differences, combined with the
biochemistry of the patient, account for the profile of efficacy,
tolerability, and safety and the risk-to-benefit ratio for the indi-
vidual. These multiple variables, some poorly understood, make
it difficult to predict a drug’s effect with certainty. Nevertheless,
knowledge of the nature of each property increases the likeli-
hood of successful treatment. The clinical effects of drugs are
best understood in terms of pharmacokinetics, which describes
what the body does to a drug,
and pharmacodynamics, which
describes
what the drug does to the body.
Pharmacokinetics and pharmacodynamics need to be seen
in the context of the underlying variability among patients with
respect to how drug effects are expressed clinically. Patients dif-
fer in their therapeutic response to a drug and the experience of
side effects. It is increasingly clear that these differences have a
strong genetic basis. Pharmacogenetics research is attempting
to identify the role of genetics in drug response.
Drug Selection
Although all U.S. Food and Drug Administration (FDA)-
approved psychotropics are similar in overall effectiveness for
their indicated disorder, they differ considerably in their phar-
macology and in their efficacy and adverse effects on individual
patients. The ability of a drug to prove effective, thus, is only
partially predictable and is dependent on poorly understood
